The goal of this program is to develop a method for specifically labelling a chemoreceptor which is hypothesized to bind covalently carbonyl compounds. Proteins which bind carbonyl substrates as Schiff bases are widespread. The proposed research will develop a specific inactivator for the amino group at the binding site of such proteins. This inactivator will be used to probe the nature of odorant binding in olfactory receptors. The inactivator is a vinylogue of acetoacetate, the natural substrate of the Schiff base-forming enzyme acetoacetic acid decarboxylase (AAD), and it is designed to inhibit the enzyme by irreversible formation of a 2-pyridone at the active site. Once the inactivator is synthesized and its reactions with simple amines explored, it will be examined as a noncompetitive inhibitor of the Schiff base-forming enzymes AAD and rabbit muscle aldolase. Once the specific nature of the inhibition is ascertained, the inactivator will be tested to see if it induces a specific anosmia for carbonyl compounds in rats. A behavioral assay will be developed to test whether olfactory detection of one class of compound (ketones) is impaired relative to another class (sulfides).